Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma

被引：15
|
作者：
Golubovskaya, Vita [1 ]
Zhou, Hua [1 ]
Li, Feng [1 ,2 ]
Berahovich, Robert [1 ]
Sun, Jinying [1 ]
Valentine, Michael [1 ]
Xu, Shirley [1 ]
Harto, Hizkia [1 ]
Sienkiewicz, John [1 ]
Huang, Yanwei [1 ]
Wu, Lijun [1 ,3 ]
机构：
[1] Promab Biotechnol, 2600 Hilltop Dr, Richmond, CA 94806 USA
[2] Hunan Univ Arts & Sci, Biol & Environm Sci Coll, Changde 415000, Peoples R China
[3] Forevertek Biotechnol, Janshan Rd, Changsha 410205, Peoples R China
来源：
BIOMEDICINES | 2021年 / 9卷 / 10期
关键词：
chimeric antigen receptor; CAR-T cells; CS1; BCMA; immunotherapy; cell therapy; tumor antigen; multiple myeloma; MATURATION ANTIGEN; RECEPTOR; THERAPY; CANCER; IMMUNOTHERAPY; SYSTEM; APRIL; BAFF; TACI; BCMA;
D O I：
10.3390/biomedicines9101422
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Multiple myeloma (MM) is a hematological cancer caused by abnormal proliferation of plasma cells in the bone marrow, and novel types of treatment are needed for this deadly disease. In this study, we aimed to develop novel CS1 CAR-T cells and bispecific CS1-BCMA CAR-T cells to specifically target multiple myeloma. We generated a new CS1 (CD319, SLAM-7) antibody, clone (7A8D5), which specifically recognized the CS1 antigen, and we applied it for the generation of CS1-CAR. CS1-CAR-T cells caused specific killing of CHO-CS1 target cells with secretion of IFN-gamma and targeted multiple myeloma cells. In addition, bispecific CS1-BCMA-41BB-CD3 CAR-T cells effectively killed CHO-CS1 and CHO-BCMA target cells, killed CS1/BCMA-positive multiple myeloma cells, and secreted IFN-gamma. Moreover, CS1-CAR-T cells and bispecific CS1-BCMA CAR-T cells effectively blocked MM1S multiple myeloma tumor growth in vivo. These data for the first time demonstrate that novel CS1 and bispecific CS1-BCMA-CAR-T cells are effective in targeting MM cells and provide a basis for future clinical trials.
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页数：11
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